Charles Craik

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Charles Craik

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Professor, School of Pharmacy
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My research interests focus on defining the roles and the mechanisms of enzymes and other challenging proteins in complex biological processes and on developing technologies to facilitate these studies. The current research in the Craik lab focuses on the chemical biology of proteolytic and protein degradation enzymes, receptors and membrane transporters. A particular emphasis of our work is on identifying the roles and regulating the activity of key proteins associated with infectious diseases, neurodegeneration and cancer. I am also interested in developing novel methods to biophysically characterize challenging proteins as well as their complexes. These studies coupled with our global substrate profiling, antibody engineering and noninvasive imaging efforts are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring and control of infectious disease, neurological disorders and cancer. This in turn is leading to the development of strategies for regulating these activities as a means of therapeutic intervention. Further study of these proteins holds promise for better understanding, rapid detection and eventual control of infectious diseases, cancer and neurodegeneration.
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  1. Sevillano N, Bohn MF, Zimanyi M, Chen Y, Petzold C, Gupta S, Ralston CY, Craik CS. Structure of an affinity-matured inhibitory recombinant fab against urokinase plasminogen activator reveals basis of potency and specificity. Biochim Biophys Acta Proteins Proteom. 2021 02; 1869(2):140562.
  2. Lohse MB, Brenes LR, Ziv N, Winter MB, Craik CS, Johnson AD. An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans. Genetics. 2020 10; 216(2):409-429.
  3. Wei J, Wang YH, Lee CY, Truillet C, Oh DY, Xu Y, Ruggero D, Flavell RR, VanBrocklin HF, Seo Y, Craik CS, Fong L, Wang CI, Evans MJ. An Analysis of Isoclonal Antibody Formats Suggests a Role for Measuring PD-L1 with Low Molecular Weight PET Radiotracers. Mol Imaging Biol. 2020 12; 22(6):1553-1561.
  4. Cogan DP, Li X, Sevillano N, Mathews II, Matsui T, Craik CS, Khosla C. Antibody Probes of Module 1 of the 6-Deoxyerythronolide B Synthase Reveal an Extended Conformation During Ketoreduction. J Am Chem Soc. 2020 09 02; 142(35):14933-14939.
  5. Wang B, Asarnow D, Lee WH, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Hu Y, Seah SGK, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A, Cheng Y, Craik CS, Wang CI. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. bioRxiv. 2020 Jul 15.
  6. Lohse MB, Gulati M, Craik CS, Johnson AD, Nobile CJ. Combination of Antifungal Drugs and Protease Inhibitors Prevent Candida albicans Biofilm Formation and Disrupt Mature Biofilms. Front Microbiol. 2020; 11:1027.
  7. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 07; 583(7816):459-468.
  8. Vasiljeva O, Menendez E, Nguyen M, Craik CS, Michael Kavanaugh W. Monitoring protease activity in biological tissues using antibody prodrugs as sensing probes. Sci Rep. 2020 04 03; 10(1):5894.
  9. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22.
  10. Dvoráková H, Leontovyc R, Machácek T, O'Donoghue AJ, Šedo O, Zdráhal Z, Craik CS, Caffrey CR, Horák P, Mikeš L. Isoforms of Cathepsin B1 in Neurotropic Schistosomula of Trichobilharzia regenti Differ in Substrate Preferences and a Highly Expressed Catalytically Inactive Paralog Binds Cystatin. Front Cell Infect Microbiol. 2020; 10:66.
  11. Harel E, Shoji J, Abraham V, Miller L, Laszik ZG, King A, Dobi D, Szabo G, Hann B, Sarwal MM, Craik CS, Vincenti F. Further Evidence That the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes. Transplantation. 2020 01; 104(1):54-60.
  12. Ivry SL, Knudsen GM, Caiazza F, Sharib JM, Jaradeh K, Ravalin M, O'Donoghue AJ, Kirkwood KS, Craik CS. The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts. Biol Chem. 2019 11 26; 400(12):1629-1638.
  13. Ravalin M, Basu K, Gestwicki JE, Craik CS. End-Binding E3 Ubiquitin Ligases Enable Protease Signaling. ACS Chem Biol. 2019 Nov 20.
  14. Harel ET, Drake PM, Barfield RM, Lui I, Farr-Jones S, Van't Veer L, Gartner ZJ, Green EM, Lourenço AL, Cheng Y, Hann BC, Rabuka D, Craik CS. Antibody-Drug Conjugates Targeting the Urokinase Receptor (uPAR) as a Possible Treatment of Aggressive Breast Cancer. Antibodies (Basel). 2019 Nov 05; 8(4).
  15. Caiazza F, Oficjalska K, Tosetto M, Phelan JJ, Noonan S, Martin P, Killick K, Breen L, O'Neill F, Nolan B, Furney S, Power R, Fennelly D, Craik CS, O'Sullivan J, Sheahan K, Doherty GA, Ryan EJ. KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment. Am J Pathol. 2019 10; 189(10):1916-1932.
  16. Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE. Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases. Nat Chem Biol. 2019 08; 15(8):786-794.
  17. Basu K, Green EM, Cheng Y, Craik CS. Why recombinant antibodies - benefits and applications. Curr Opin Biotechnol. 2019 Mar 05; 60:153-158.
  18. Harel E, Shoji J, Abraham V, Miller L, Laszik Z, Thurison T, King A, Olshen A, Leung J, Szabo G, Hann B, Høyer-Hansen G, Craik CS, Vincenti F. Identifying a potential biomarker for primary focal segmental glomerulosclerosis and its association with recurrence after transplantation. Clin Transplant. 2019 Jan 28; e13487.
  19. Butler VJ, Cortopassi WA, Argouarch AR, Ivry SL, Craik CS, Jacobson MP, Kao AW. Progranulin Stimulates the in vitro Maturation of pro-Cathepsin D at Acidic pH. J Mol Biol. 2019 Jan 25.
  20. Damalanka VC, Han Z, Karmakar P, O'Donoghue AJ, La Greca F, Kim T, Pant S, Helander J, Klefström J, Craik CS, Janetka JW. Discovery of Selective Matriptase and Hepsin Serine Protease Inhibitors: Useful Chemical Tools for Cancer Cell Biology. J Med Chem. 2018 Dec 20.
  21. Schneidman-Duhovny D, Khuri N, Dong GQ, Winter MB, Shifrut E, Friedman N, Craik CS, Pratt KP, Paz P, Aswad F, Sali A. Predicting CD4 T-cell epitopes based on antigen cleavage, MHCII presentation, and TCR recognition. PLoS One. 2018; 13(11):e0206654.
  22. Li X, Sevillano N, La Greca F, Hsu J, Mathews II, Matsui T, Craik CS, Khosla C. Discovery and Characterization of a Thioesterase-Specific Monoclonal Antibody That Recognizes the 6-Deoxyerythronolide B Synthase. Biochemistry. 2018 Oct 30; 57(43):6201-6208.
  23. Moroz A, Lee CY, Wang YH, Hsiao JC, Sevillano N, Truillet C, Craik CS, Fong L, Wang CI, Evans MJ. A Preclinical Assessment of 89Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with 89Zr-C4. Bioconjug Chem. 2018 Oct 17; 29(10):3476-3482.
  24. Debela M, Magdolen V, Skala W, Elsässer B, Schneider EL, Craik CS, Biniossek ML, Schilling O, Bode W, Brandstetter H, Goettig P. Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin. Sci Rep. 2018 Jul 16; 8(1):10705.
  25. Li X, Sevillano N, La Greca F, Deis L, Liu YC, Deller MC, Mathews II, Matsui T, Cane DE, Craik CS, Khosla C. Structure-Function Analysis of the Extended Conformation of a Polyketide Synthase Module. J Am Chem Soc. 2018 05 30; 140(21):6518-6521.